Trial document




drksid header

  DRKS00009416

Trial Description

start of 1:1-Block title

Title

Rescue treatment with the monoclonal anti CD20-antibody Obinutuzumab (GA101) in combination with PixantrOne for the treatment of patients with relapsed Aggressive B-cell Lymphoma

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

ETN-1: GOAL

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

[---]*

end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

Treating a relapsed aggressive lymphoma is a challenge. A lot of patients are treated with high-dose chemotherapies to annihilate the disease. In this trial we aim to treat patients, who are not eligible for this kind of treatment due to their age or other issues or who have been treated unsuccessfully.

In this situation a lot of treatment options have shown good results, however those generally did not last long. An improvement of the situation is much needed and using new drugs might lead to improvement.
In the scope of this trial patients with a histologically proven relapse of a diffuse large B-cell Lymphoma, follicular lymphoma grade IIIB or transformed indolent lymphoma will be included.

All patients will receive a combination of two drugs, which both have shown good efficacy in malignant lymphoma and that both have been approved for use in humans.
Pixantrone (Pixuvri®) is approved for the treatment of aggressive lymphoma, although not in combination with other substances. Obinutuzumab (Gazyvaro®) is a monoclonal antibody, which has shown significantly better results than Rituximab in other lymphoma entities.

The combination of both substances could therefore be a promising treatment option for patients with relapsed aggressive lymphoma. The aim of this trial is to evaluate the efficacy of this combination under close supervision. Further objectives are to evaluate the safety of the combination as well as the time until the next relapse and the overall survival time.

The therapy consists of up to 6 cycles of both trial drugs. One cycle lasts 28 days; the whole therapy will last up to 24 weeks.

After the end of the therapy, patients will be followed up every 3 months for two years. CTs will be performed every 6 months, to assess the treatment outcome. Subsequent follow up visits will be scheduled in longer intervals and will not include CT assessments.

In July 2016 the protocol was amended as follows: The application of new assays for high sensitive troponin I (TNI) in numerous clinics frequently leads to slightly elevated TNI-values, without there being an immediate underlying cardiological problem. Therefore inclusion criterion No 6 was rephrased. Furthermore changes in both IBs (Obinutizumab and Pixantrone) were implemented into the protocol and the informed consent form. The amendment was approved by the ethics committee on 21/07/2016.

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

The purpose of this study is to evaluate the overall response rate of Obinutuzumab (GA101) in combination with Pixantrone in patients with relapsed aggressive B-cell lymphoma. 70 patients with diffuse large B-cell lymphoma, follicular lymphoma grade IIIB or transformed indolent lymphoma will receive up to 6 cycles of the described combination regimen. Follow up visits are scheduled for up to 3 years

end of 1:1-Block scientific synopsis
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00009416
  •   2015/10/13
  •   2015/07/06
  •   yes
  •   Approved
  •   837.164.15 (9932), Ethik-Kommission bei der Landesärztekammer Rheinland-Pfalz
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  •   U1111-1174-7946 
  •   2014-004780-21 
  •   NCT02499003  (ClincalTrials.gov)
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   C83.3 -  Diffuse large B-cell lymphoma
  •   C82.4 -  Follicular lymphoma grade IIIb
  •   C85.1 -  B-cell lymphoma, unspecified
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   Obinutuzumab (GAZYVARO™): 1000 mg flat dose on day 1, 8, 15 of cycle one and day 1 of subsequent cycles
    (first dose may be split over 2 days if investigators anticipates a high risk of infusion related reactions =IRR)

    and

    Pixantrone (Pixuvri®): 50 mg/m² Pixantrone on day 1,8,15 of each 28 d cycle (Equiv. to 85 mg/m² Pixantrone dimaleate)
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Interventional
  •   [---]*
  •   Single arm study
  •   Open (masking not used)
  •   [---]*
  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   II
  •   Yes
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

The primary endpoint is the ORR of the regimen at cycle 6 or the individual treatment end tested in the entire cohort of patients (30 weeks).
The response to treatment is measured by results of computer tomography (CT) for measurable lesions and evaluation for non-measurable lesions after cycle 6 or at the individual end of treatment.

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

Secondary Outcome

- Safety of the combination treatment as measured by the rate of adverse events, which reflects tolerability of the treatment (30 weeks)
- Percentage of patients completing the entire trial treatment (30 weeks)
- Evaluation of best response to trial treatment as measured as best response either during or post the entire treatment (up to 3 years)
- Progression free survival (up to 3 years)
- Overall survival (up to 3 years)
- ORR in separate GCB vs. non GCB-analysis is planned (GEP-profiling) (30 weeks)

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   Germany
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   Actual
  •   2015/08/14
  •   70
  •   Multicenter trial
  •   National
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional Inclusion Criteria

- Patients aged ≥ 18 years
- Histologically proven diagnosis of diffuse large cell B-cell lymphoma, follicular lymphoma IIIB or transformed indolent lymphoma according to the World Health Organization classification (central pathology review)
- Relapsed disease
- Eastern Cooperative Oncology Group [ECOG] performance Status ≤2, unless tumor associated
- Adequate cardiac reserve: Serum Troponin level must be consistent with no significant acute or chronic myocardial damage and there should be no evidence of symptomatic disease
- No curative option available
- At least 1 measurable tumor mass (>1.5 cm x >1.0 cm) or bone marrow infiltration
- Adequate bone marrow reserve: Platelets of at least 100.000/µl (in case of extensive BM-infiltration 75.000/µl may be acceptable after discussion with the coordinating investigator), absolute neutrophil count of at least 1000/µl. Adequate hepatic and renal function: Alanine aminotransferase <2.5 x upper limit of normal (ULN); Aspartate aminotransferase <2.5 x ULN, total bilirubin <1.5 x ULN
- No active Hepatitis B or C or HIV-infection
- Measured or calculated creatinine clearance >30 mL/min
- Fresh tumor biopsy or archived tissue available
- Ability of patients to understand nature, importance and individual consequences of clinical trial.
- Signed informed consent
- Women post-menopausal for more than two years can participate in the trial. Women with childbearing potential can only participate, if they are surgically sterile or a negative pregnancy test (serum or urine) is available before trial and they are willing to practice a highly effective and medically accepted contraception method during trial and for a period of 18 months post-treatment. Reliable contraception comprises systematic contraceptives (oral, implant, injection) or diaphragm / condoms / intrauterine devices (IUP) with spermicide.
- Male patients are advised to use contraceptive methods (preferably barrier) during treatment and for a period of 6 months post-treatment

end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

Exclusion Criteria

- Lymphoma other than DLBCL, FL IIIB, transformed indolent NHL
- CNS involvement (brain MRI is required only in cases of clinically suspicious involvement)
- Pregnant or breast-feeding women
- Severe concomitant disease (e.g. uncontrolled arterial hypertension, heart failure (NYHA III-IV), uncontrolled diabetes mellitus, pulmonary fibrosis, uncontrolled hyperlipoproteinaemia)
- Myocardial infarction within the last 6 months
- Active uncontrolled infections including HIV-positivity, active Hepatitis B or C
- Vaccination with live vaccine within last 4 weeks
- Mental status precluding patient’s compliance
- Known CD20 negativity
- Diagnosed or treated for a malignancy other than NHL except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, DCIS of the breast, or other solid tumors curatively treated with no evidence of disease for >3 years, or prostate cancer with a life expectancy of more than 2 years
- Treatment with any approved anticancer agent within last 2 weeks. Any agents must have been stopped at least 2 weeks prior to day 1 of GOAL treatment and all treatment related adverse events must have returned to Grade 1.
- Prior exposition to Obinutuzumab or Pixantrone
- History of hypersensitivity to medicinal products with similar chemical structure as the trial medication
- Active participation in other interventional clinical trials during the present clinical trial or within the last 2 weeks prior to treatment initiation. Concurrent participation in non-treatment studies is not excluded
- Medical or psychological conditions that would jeopardize an adequate and orderly completion of the trial.

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
    • Langenbeckstr. 1
    • 55131  Mainz
    • Germany
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address other
    • Interdisziplinäres Zentrum Klinische Studien (IZKS), Universitätsmedizin der Johannes Gutenberg-Universität Mainz
    • Langenbeckstr. 1
    • 55131  Mainz
    • Germany
    end of 1:1-Block address other
    start of 1:1-Block address contact other
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact other
  • start of 1:1-Block address scientific-contact
    • III. Med. Klinik, Universitätsmedizin der Johannes Gutenberg-Universität Mainz
    • Mr.  Univ.-Prof. Dr. med.  Georg  Heß 
    • Langenbeckstr. 1
    • 55131  Mainz
    • Germany
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • III. Med. Klinik, Universitätsmedizin der Johannes Gutenberg-Universität Mainz
    • Mr.  Univ.-Prof. Dr. med.  Georg  Heß 
    • Langenbeckstr. 1
    • 55131  Mainz
    • Germany
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • ROCHE Pharma AG
    • Emil-Barell-Str. 1
    • 79639  Grenzach-Wyhlen
    • Germany
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact materialSupport
  • start of 1:1-Block address otherSupport
    • CTI Life Sciences Limited
    • 6 - 9 The Square, Stockley Park
    • UBl 1 lFW  Uxbridge
    • United Kingdom
    end of 1:1-Block address otherSupport
    start of 1:1-Block address contact otherSupport
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact otherSupport
  • start of 1:1-Block address otherSupport
    • Servier Affaires Médicales;
    • 35 rue de Verdun
    • 92284  SURESNES CEDEX
    • France
    end of 1:1-Block address otherSupport
    start of 1:1-Block address contact otherSupport
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact otherSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting ongoing
  •   [---]*
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

  • [---]*
end of 1:n-Block publications
* This entry means the parameter is not applicable or has not been set.